American 

College of Physicians 
Internal Medicine Meeting 2021: Virtual Experience

Thyroid Disorders: What’s New?

Faculty and Disclosure Information
Professor:
Douglas S. Paauw, MD, MACP
Nothing to Disclose.

Clinical questions to be addressed:
1. What is the appropriate management of thyroid nodules?
2. What is the correct dosing, pitfalls, and options for thyroid replacement therapy?
3. What should you think of when your patient with previously well replace hyperthyroidism has 
arising TSH?
4. What is the latest on management and monitoring of subclinical hypo‐ and hyperthyroidism?

Posted Date: March 29, 2021

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 Thyroid Pearls and Update 2021

Doug Paauw MD, MACP

Disclosure of Financial Relationships

Douglas Paauw
Has no relationships with any entity
producing, marketing, re-selling, or
distributing health care goods or services
consumed by, or used on, patients.

© 2021 American College of Physicians. All rights reserved. 1

 What Are The Symptoms and
Presentations of Hypothyroidism?

Symptoms of Hypothyroidism
Fatigue
Constipation
Slight weight gain
Dry skin
Cold intolerance
Muscle aches
Hoarseness
These are pretty much seen in most patients we
see in primary care 

© 2021 American College of Physicians. All rights reserved. 2

 Physical Findings
Periorbital edema
Diastolic hypertension
Bradycardia
Edema
Goiter
Delayed relaxation phase on DTR
Large tongue
Carpal tunnel syndrome

A Few Unexpected Presentations

Sleep Apnea
Inability to get off ventilator
Pericardial effusion
Worsening hypotension
Alterations in sense of taste

© 2021 American College of Physicians. All rights reserved. 3

 Lab abnormalities
Hyperlipidemia
Hyponatremia
Increased CK, AST

A 36 yo woman comes to clinic for evaluation of

fatigue. She has not been sleeping well and is too
tired to get out of the bed in the morning. She has
no other symptoms. Physical exam is normal. Labs:
TSH 6 (NL .4-4.5) , free T4 1.2 (NL) HCT 39. What
would you recommend?
A) Start levothyroxine 25 mcg daily
B) Start levothyroxine 50mcg a day
C) Start levothyroxine 75 mcg a day
D) Start levothyroxine 100 mcg a day
E) Check antithyroid antibodies

© 2021 American College of Physicians. All rights reserved. 4

 Should I Treat Subclinical
Hypothyroidism, and If So ,
When?

Subclinical Hypothyroidism
Defined as elevated TSH with a normal free T4
1/3 to ½ progress to overt hypothyroidism
Initial TSH level is important, risk of progression
greater if TSH>10 (1)
Initial TSH between 5.5 and 10 normalizes without
treatment in 62% (2)
Presence of thyroid antibodies increases chance of
progression
1) J Clin Endocrinol Metab. 2002;87(7):3221.

2) Arch Intern Med 2007;167(14):1533

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© 2021 American College of Physicians. All rights reserved. 5

 Does Treating Subclinical Hypothyroidism
Change Symptoms?
To assess the effects of thyroid hormone replacement
for subclinical hypothyroidism.
All studies had to be randomized controlled trials
comparing thyroid hormone replacement with placebo or
no treatment in adults with subclinical hypothyroidism.
Minimum duration of follow-up was one month.
Levothyroxine replacement did not improve survival,
improve quality of life or improve symptoms.
Cochrane Database Syst Rev. 2007
JAMA 2018 ;320(13): 1349

11

Who Should Receive Treatment?

Treat if TSH >10 (higher rate of
progression and possible increased
cardiac risk*)
Strongly consider treatment in non
elderly patients with positive thyroid
peroxidase antibodies
Treat pregnant woman, and women
attempting to get pregnant.
* Controversial

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© 2021 American College of Physicians. All rights reserved. 6

 What if My Patient Really
Wants To Be Treated?
Shared decision making
The risk of therapy is minimal in patients
who are followed (can catch over
replacement before it causes problems)
You might get placebo response
Would be cautious in treating the
elderly, where the risks are likely higher

13

A 33 yo woman with a hx of hypothyroidism

presents for follow up. She reports that she has
been trying to get pregnant and this morning
confirmed a 2nd positive home pregnancy test.
She is currently taking 100 mcg of
levothyroxine, with a TSH of 3.0 measured 2
months ago. What do you recommend?
A) Repeat TSH in 6 weeks
B) Increase levothyroxine to 9 tablets a week
C) Decrease levothyroxine to 88 mcg daily
D) Continue on same dose of levothyroxine

14

© 2021 American College of Physicians. All rights reserved. 7

 Pregnancy Changes Influencing
Thyroid
Major
physiologic changes during
pregnancy
●An increase in serum thyroxine-binding globulin
(TBG)
●Stimulation of the thyrotropin (TSH) receptor by
human chorionic gonadotropin (hCG)

15

Complications of Maternal
Hypothyroidism
●Preeclampsia and gestational hypertension*
●Placental abruption*
●Preterm delivery, including very preterm delivery (before 32
weeks)*
●Low birth weight
●Increased rate of cesarean section
●Postpartum hemorrhage
●Perinatal morbidity and mortality
●Neuropsychological and cognitive impairment in the child
*Occurs in subclinical hypothyroidism

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© 2021 American College of Physicians. All rights reserved. 8

 Thyroid Dosing in Early Pregnancy
60 women with treated hypothyroidism seeking pregnancy.
Once pregnant, women were randomized to increase l-T(4) by
either two tablets/wk (group A) or three tablets/wk (group B).
Increasing the l-T(4) dose once pregnant (regardless of study
arm) prevented TSH elevation over 5.0 mIU/liter throughout the
first trimester and replicated physiological changes of
pregnancy.
The early l-T(4) increase caused TSH suppression below 0.5
mIU/liter in eight of 25 women in group A compared with 15 of
23 women in group B (P<0.01).
J Clin Endocrinol Metab 2010;95 (7): 3234

17

You are going through your labs from yesterday

and find that the TSH result on your overweight (
80 kg) 22 yo woman with a goiter that you saw
yesterday is 44. What will you advise her?
A) To return to clinic and have a free T4 drawn
B) Start Levothyroxine 25 mcg a day for 4 weeks
C) Start Levothyroxine 50 mcg a day for 4 weeks
D) Start levothyroxine 125 mcg a day

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© 2021 American College of Physicians. All rights reserved. 9

 What is the Appropriate Starting
Dose for Thyroid Replacement?

19

The Starting Dose of Levothyroxine

in Primary Hypothyroidism
Treatment
Prospective, randomized ,double blind trial full starting
dose of L thyroxine vs 25 mcg starting dose
increasing every 4 weeks, in newly Dx patients without
cardiac sx
50 patients randomized. Euthyroidism reached in 13
patients in the full dose group at 4 weeks vs 1 in the
low dose, 19 vs 3 at 8 weeks and 19 vs 9 at 12 weeks
No symptoms from replacement in either group
Arch Int Med 2005; 165: 1714-1720

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© 2021 American College of Physicians. All rights reserved. 10

 Dose Needed of
Levothyroxine
1.6 mcg/kg daily is the average dose needed
This is impacted by lean body mass. 1.76
mcg/kg daily BMI<25, compared to 1.27 mcg/kg
for BMI 35-39 *
Start at low doses (12.5 to 25 mcg/day) for
patients with known CAD or the elderly, target
TSH should be 4-6 in the elderly
*Thyroid. 2019;29(11):1558. Epub 2019 Oct 1.

21

My Patient Wants to Take

Desiccated Thyroid

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© 2021 American College of Physicians. All rights reserved. 11

 What is the Deal With
Desiccated Thyroid?
Has T4 to T3 ratio of 4:1, physiologic
ratio is 13:1 to 16:1
Some patients may want it because it is
“natural”, others may want it because
they like it

23

Desiccated Thyroid vs
Levothyroxine
Randomized, double blind, cross over study
desiccated thyroid and levothyroxine
48.6% preferred desiccated thyroid, 18.6%
preferred levothyroxine and 32.9% had no
preference
No significant improvement in quality of life

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© 2021 American College of Physicians. All rights reserved. 12

 Is There Any Role for
Combination T4/T3 Therapy?

25

Bottom Line From Last

Guidelines Published in 2014
Levothyroxine should remain the standard for
treating hypothyroidism
No consistently strong evidence for the
superiority of alternative
preparations/combination therapy over
monotherapy with levothyroxine

THYROID Volume 24, Number 12, 2014

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© 2021 American College of Physicians. All rights reserved. 13

 T4 vs Combination Therapy
for Hypothyroidism
Randomized trials that compared the effectiveness of T(4)-T(3)
combination vs. T(4) monotherapy for the treatment of clinical
hypothyroidism in adults were included.

11 studies, in which 1216 patients were randomized. No

difference was found in the effectiveness of combination vs.
monotherapy in any of the following symptoms: bodily pain,
depression , anxiety , fatigue , quality of life, body weight, total
serum cholesterol, triglyceride levels, low-density lipoprotein, and
high-density lipoprotein. Adverse events did not differ between
regimens.
J Clin Endocrinol Metab. 2006;91(7):2592.

27

Any Subgroups Who Might

Benefit?
Patients post thyroidectomy who have
symptoms despite adequate TSH response
Patients S/P radioactive ablation of the thyroid
Use 13:1 to 16:1 T4/T ratio- 5 mcg Cytomel
tablets are usually used to allow this titration
Do not use combination therapy in pregnant
women (avoid in the elderly as well)

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© 2021 American College of Physicians. All rights reserved. 14

 How Should I Manage A Patient
on Previously Adequate Thyroid
Replacement Who Has a Rising
TSH?

29

The Effects of Evening vs

Morning Thyroxine Ingestion
Patients were studied on two occassions , on a stable
regimen of morning thyroxine administration, and two
months after switching to night time thyroxine dosing.
12 women on thyroxine replacement for
hypothyroidism who were not on any interfering meds
were studied
24 hour average TSH values were 5.1 when the
women were on morning administration vs 1.2 when
on evening administration ( p<.01)
Clin Endo 2007;66: 43-48.

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© 2021 American College of Physicians. All rights reserved. 15

 Effect of Gastric PH on Thyroid
Absorption
Dose of thyroxine evaluated in 248 patients
receiving thyroxine with multinodular goiter
53 patients had H Pylori gastritis and 60 had
atrophic gastritis. 135 had no gastritis and served as
control group. Ten patients received Omeprazole for
GERD
Daily requirement for thyrovine was 22-34% higher
for patients with H Pylori infection or atrophic
gastritis. In the omeprazole treated patients
thyroxine dose needed to be increased by 37%
NEJM 2006;354: 1787-95.

31

Work Arounds for Patients on

PPI’s/Atrophic Gastritis
Increase dose
Gel cap or liquid formulations *

• Endocr Pract. 2014 Mar;20(3):e38-41.

• J Clin Endocrinol Metab. 2014;99(12):4481.

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© 2021 American College of Physicians. All rights reserved. 16

 What Should You Do With A Patient
On Thyroxine With A Rising TSH?
Assess compliance
Are they taking it on empty stomach
Taking FeSo4?
Taking CaCo3?
Taking Estrogen or raloxifene?
Taking sucralfate/cholestyramine?
Taking PPI or H2 blocker
Could they have achlorhydria?
Could the patient have sprue?

33

A 47 yo woman with a history of hashimoto’s

thyroiditis, celiac disease and pernicious anemia
presents with fatigue and intermittent
palpitations. She has been taking levothyroxine
125mcg X 10 years. Her TSH which was 2 one
year ago is now .03. Her dose is reduced to
100mcg and a repeat TSH is .03 with a free T4
of 1.8 (Nl.6-1.2). PE: BP 100/60 P 80 T 37
Exam is normal

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© 2021 American College of Physicians. All rights reserved. 17

 What is the most likely
diagnosis?
A) Hashitoxicosis
B) Grave’s disease
C) Patient is taking extra thyroid hormone
D) Patient is taking biotin
E) Patient is taking lithium

35

Biotin And Thyroid Assays

High dose biotin can make thyroid tests look like
patient is hyperthyroid (decrease in TSH, elevation of
free T4 assay)
The abnormality in lab accuracy is caused by
interference of high dose biotin with the biotin-
streptavidin chemistry of the immunoassay
Washout period 10 hours-2 days
Cureus. 2018 Jun; 10(6): e2845.
Nutrition. 2019 Jan;57:257-258.
Medicine (Baltimore). 2020 Feb;99(9):e19232.

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© 2021 American College of Physicians. All rights reserved. 18

 Drug Induced Hypothyroidism
Amiodarone (it can also cause
hyperthyroidism)
Lithium

37

A Few More Pearls

If you are not sure if a patient is non adherent vs
has an absorption problem, can give patient
weekly thyroid dose all at once, and check free
T4 2 hours later- should increase by 50% if
absorption is normal *
In patients with adherence difficulties, can give
levothyroxine as a single weekly dose
*Eur J Endocrinol. 2013;168(6):913.

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© 2021 American College of Physicians. All rights reserved. 19

 Thyroid Nodules

39

A 35 yo woman has a CT scan done of her neck

because of difficulty swallowing. She had low grade
fevers, and severe sore throat, raising concern for
retropharyngeal abscess. The CT does not show that,
but does show three thyroid nodules. Ultrasound of
the nodules shows an 8mm nodule (U4 – suspicious),
a 1.5 cm nodule (U2- benign) and an 8 mm nodule
(U3- indeterminate). What do you recommend?
A) FNA of all 3 nodule
B) FNA of 2 nodules
C) FNA of 1 nodule
D) No FNA, Ultrasound follow up in 1 year

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© 2021 American College of Physicians. All rights reserved. 20

 Who Should Receive FNA of
Thyroid Nodules?
Ultrasound high and intermediate suspicion
pattern >1cm
Low suspicion pattern >1.5 cm
Very low suspicion pattern >2cm
Benign pattern FNA not required

Thyroid. 2016. PMID: 26462967

41

How Should You Follow

Thyroid Nodules?
Nodules with high suspicion US pattern: repeat US and US-
guided FNA (if >1cm) within 12 months.
Nodules with low to intermediate suspicion US pattern: repeat
US at 12–24 months.
Nodules with very low suspicion US pattern – not clear if they
need continued US, if you choose to do so, should be >24
months
If a nodule has undergone repeat US-guided FNA with a
second benign cytology result, US surveillance for continued
risk of malignancy is no longer indicated.
Thyroid. 2016. PMID: 26462967

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© 2021 American College of Physicians. All rights reserved. 21

 A 87 yo woman is involved in a MVC injuring her
neck. She has a CT scan looking at her C spine,
which is fine. You are called by the radiologist
because CT shows a 1cm X 1 cm L lobe thyroid
nodule. TSH 1.2 PMH: CHF, CKD (GFR 30). What
will you do?
A) Thyroid ultrasound
B) Order ultrasound guided needle bx of thyroid
nodule
C) Thyroid RIU
D) Repeat CT scan in 6 months
E) Nothing

43

Thyroid Nodules
Don’t work up in the elderly (especially in those
over 80)
USPTF has recommended against screening
thyroid PE
If a nodule is found in a non elderly patient,
ultrasound eval for high risk features, needle
biopsy if high risk features on ultrasound

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© 2021 American College of Physicians. All rights reserved. 22

 Hyperthyroidism

45

Symptoms of Hyperthyroidism
Heat intolerance
Weight loss (non elderly)
Tremor
Anxiety
Hyperdefecation
Dyspnea
Increased sweating
Muscle weakness (especially proximal)
Amenorrhea
Polyuria

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© 2021 American College of Physicians. All rights reserved. 23

 Signs of Hyperthyroidism
Lid lag
Tremor
Tachycardia
Goiter
Proximal muscle weakness
Hypereflexia
Gynecomastia (men)
Onycholysis
Hair thinning

47

Abnormal Labs in Hyperthyroidism

Increased calcium
Elevated alkaline phosphatase
Low total and HDL cholesterol
Impaired glucose tolerance

48

© 2021 American College of Physicians. All rights reserved. 24

 Interesting Presentations of
Hyperthyroidism

High output CHF

Osteoporosis
New atrial fibrillation
Thyrotoxic periodic paralysis

49

Hyperthyroidism: Causes
Grave’s Disease
Toxic Multinodular Goiter
Toxic Adenoma
Thyroiditis (e.g. Post-partum,
granulomatous, lymphocytic, radiation
or Hashimoto’s disease in early stage)
Ectopic/Exogenous hormone
Medications

50

© 2021 American College of Physicians. All rights reserved. 25

 A 30 yo woman lab tech with presents with concerns
of multiple soft stools/day . She has also noticed
some decreased ability to rise from squatting position.
PMH Depression, GERD and Vitiligo. PE: BP 150/90
P 100 BMI 22 Neck- no adenopathy or thyromegaly.
Ext- tremor present. Labs- TSH<.01 ,FT4 2.3 (Nl .6-
1.6)
RAIU 2% at 24 hours (very low)
What is the most likely diagnosis?
A) Hyperfunctioning thyroid adenoma
B) Graves disease
C) Toxic multinodular goiter
D)Thyroid ingestion
E) Trophoblastic disease

51

Radioactive Iodine Uptake

Normal Range: 10-30% at 6 hours 80% uptake in Grave’s disease

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© 2021 American College of Physicians. All rights reserved. 26

 Radioactive Iodine Uptake

“Toxic” Adenoma Thyroiditis

53

RAIU and Hyperthyroidism

Low Uptake High Uptake
Thyroiditis Graves
Lymphocytic/postpartum Hyperfunc adenoma
Thyroid hormone ingestion Toxic MNG
Struma ovarii Trophoblasticdisease
Metastatic follicular

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© 2021 American College of Physicians. All rights reserved. 27

 Diagnostic Approach
Hyperthyroidism
If history/exam suggest clear diagnosis
(Graves ophthalmopathy, patient ingesting
thyroid hormone, physical exam signs/sx of
acute thyroiditis) – you have diagnosis
If not certain from history/exam- check Trab, if
negative then check RIU (will separate
thyroiditis from early Graves’ disease without
antibodies yet)

55

Pretibial Myxedema

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© 2021 American College of Physicians. All rights reserved. 28

 A 84 yo woman presents with some lower
extremity edema. Other medical problems
include depression and CRI. A “Lab Rodeo”
is done and the only abnormality is a TSH of
.15 (NL .4-4.5) with a normal free T4 and a
normal T3. What do you recommend?
A) Repeat TSH in 3-6 months
B) DXA and Thyroid RIU
C) Start B Blocker
D) Treatment of hyperthyroidism

57

Subclinical Hyperthyroidism
Definition- low TSH with normal Ft4 and T3
Most common cause is over replacement with thyroid
hormone
Progression to overt hyperthyroidism 6% first year,
and rare after that (about .5%)
It is much more common to progress in patients with
Grave’s disease or nodular goiter
Much rarer in elderly patients, especially if TSH is .1-
.4, progression <1%/ year
If TSH is<.1 likelihood of progression is much higher

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© 2021 American College of Physicians. All rights reserved. 29

 Subclinical Hyperthyroidism
Increased risk of atrial fibrillation
Low bone density

59

Subclinical Hyperthyroidism
Patients >65 and those with heart disease or
osteoporosis with TSH <.1 should be treated
In others who persistently have TSH <.1,
treatment should be considered in
asymptomatic individuals
For patients with TSH .1-.4, observation with
repeat testing is reasonable.

Thyroid 2016; Vol. 26, No. 10;1343

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© 2021 American College of Physicians. All rights reserved. 30